This proposal is designed to create technology that can be rapidly applied to the generation of novel vaccines against biodefense threat agents. Antigens that have the potential to provide protection against a biodefense threat have been identified or are emerging from independent research. This SBIR proposal is designed to identify technology platforms that can rapidly convert such antigenic genes into potent vaccines for clinical testing. Existing adenovirus vaccine platforms promote strong balanced immune responses [including mucosal responses] and there is a wealth of existing know-how for GMP production, manufacturing and quality testing. The objectives of this SBIR proposal address a potential weakness in current adenovirus vector technology based on Adenovirus serotype 5 (Ad5). Previous exposure and resulting immune response to Ad5 viruses or vectors can limit the potency of Ad5 vaccine vectors. Consequently, immunization for HIV may well render Ad5 based vectors less potent for other applications. A central goal of this application is to broaden the applicability of adenovirus vector technology by establishing and testing new Advector vaccine technology platforms. We, and others,are currently exploring non-Ad5 technology for vaccine applications. Unfortunately for biodefense, these first non-Ad5 technologies will also be used in the generation of HIV or malaria vaccines. In this application, we propose to develop additional non-Ad5 and non-Ad35 technologies for biodefense vaccine application. This SBIR is aligned with the effort to produce broadly applicable or "Universal," biodefense technology. [unreadable] [unreadable]